KMT2D基因变异所致歌舞伎综合征1例
A case of Kabuki syndrome caused by KMT2D gene mutation
董佳宁 1张飘飘 2徐芬芬 2赵红洋2
作者信息
- 1. 山东第一医科大学附属济南市中心医院儿科,山东 济南 250013;山东第一医科大学 山东省医学科学院,山东 济南 250117
- 2. 山东第一医科大学附属济南市中心医院儿科,山东 济南 250013
- 折叠
摘要
目的 探讨歌舞伎综合征(Kabuki syndrome,KS)临床表型及基因变异类型和基因检测诊断.方法 对患儿进行外周血家系全外显子测序,并通过Sanger DNA测序验证.结果 先证者为6 岁5 个月的女性患儿,表现为特殊面容、发育迟缓、惊厥发作、脑电图异常、反复中耳炎病史等.患儿外周血家系全外显子测序显示,KMT2D基因(NM003482)c.3094del(p.Leu1032TrpfsTer24)存在变异.该变异为移码变异.Sanger DNA测序结果显示患儿父亲、母亲均未携带该变异,表明该变异为新发变异.根据美国医学遗传学与基因组学学会变异解读标准,该基因变异分类为 PVS1+PS2+PM2,属于致病性变异.结论 患儿确诊为由KMT2D基因变异导致 KS1 型,为常染色体显性遗传.本研究结果表明,对于疑似KS者应做到早诊断、早干预;对于已知基因无变异的患者,应根据国际共识标准进行临床诊断,并进行随访和遗传咨询.本研究进一步丰富了KS基因变异谱,为该病的诊断和遗传咨询提供依据.
Abstract
Objective To explore the clinical phenotype,gene variant types and diagnosis of genetic testing of Kabuki syndrome(KS).Methods The whole exon sequencing(WES)of peripheral blood of a child was performed and veri-fied with Sanger DNA sequencing.Results The proband was a girl aged 6 years and 5 months,who showed special facial features,developmental delay,convulsive seizures,abnormal electroencephalogram,and recurrent otitis media.WES showed KMT2D gene(NM003482)c.3094del,(p.Leu1032TrpfsTer24)mutation,which was a frameshift muta-tion.Sanger DNA sequencing results showed that the father and mother of the proband did not carry the KMT2D muta-tion,indicating that this mutation was a de novo one.According to the(American College of Medical Genetics and Ge-nomics,ACMG)mutation interpretation standard,the mutation was classified as PVS1+PS2+PM2,which was a patho-genic mutation of KS.Conclusion The child was diagnosed with KS type 1 caused by KMT2D gene mutation,which was autosomal dominant.Our study revealed that early diagnosis and intervention should be performed for suspected KS;for patients with no known genetic variation,clinical diagnosis should be confirmed according to international con-sensus criteria,follow-up and genetic counseling.This study enriched the genetic mutation spectrum of KS and provided a basis for the diagnosis and genetic counseling of this disease.
关键词
歌舞伎综合征/KMT2D基因/特殊面容/家系基因检测Key words
Kabuki syndrome/KMT2D gene/Special facial features/Trio-whole genome testing引用本文复制引用
基金项目
"泉城学者"建设工程项目(P-20230825-0025)
出版年
2024
NETL
NSTL
万方数据